1. Field of the Invention
The present invention relates to a pharmaceutical kit, methods for cancer treatment via intracavity delivery and for preparing a metal nanoparticle-antibody fragment conjugate.
2. Description of Related Art
In recent years, surface plasmonic nanoparticles have been commonly used due to the unique and tunable optical properties. The wavelength absorbed by nanoparticles depends on their size and shape. Many researches have been conducted on the application of gold nanoparticles (GNPs) in cancer diagnosis or therapy because GNPs have excellent photothermal properties, such as surface plasmon resonance, biological compatibility, and etc. Surface plasmonic gold nanoparticles have been proved to be more nontoxic than other kinds of nanoparticles for cancer treatment and detection, such as core-shell nanoparticles, magnetic nanoparticles and quantum dots where silica is commonly used in the cores thereof. In addition, GNPs are characterized by high chemical stability, high affinities to biomolecules, and non-cytotoxicity, and can be used as agents for cancer detection and therapy.
On these grounds, GNPs including gold nanorods and gold/silica nanoshells have been recently used as both imaging and therapy agents for treating a number of cancers, such as breast cancer, brain tumor, oral cavity cancer and prostate cancer with similar absorption wavelengths of near infrared (NIR). For the examination of cell uptake, GNPs with a spherical shape and a diameter of 50 nm have the best uptake capacity for mammalian cells compared with those of other sizes (14, 30, 74, and 100 nm) or shapes (e.g. a rod shape) (40×14 nm and 74×14 nm). Thermal therapies cause necrosis in cancer cells by rupturing membranes and releasing digestive enzymes. Currently, a variety of heat sources, such as ultrasound, microwaves, and laser light in thermal therapy, have been employed.
Although various hyperthermia techniques have been widely employed in treating cancers, such techniques involve heating tissues along the course and are likely to cause damages to normal tissues due to the lack of specificity of the heating. The aforementioned cancers often develop from cells on the inner surfaces of the organs. In such cases, a doctor sometimes resects the carcinoma only rather than the entire organ to maintain the function of the organ. Unfortunately, the recurrence rate may increase due to the foregoing operation, and thus an adjuvant therapy is required to reduce the recurrence rate. For example, bladder carcinoma is a relatively common malignancy in the urinary tract. There are more than 90% of bladder carcinoma patients have primary transitional cell carcinoma (TCC) in their bladders. A doctor sometimes resects the carcinoma only (e.g. transurethral resection of bladder tumor (TUR-BT) for superficial urinary bladder cancer) rather than the entire organ to maintain the function of the organ. However, the recurrence rate of urinary bladder cancer is about 70% in 5 years after the TUR-BT operation, and an adjuvant therapy, such as intravesical Bacillus Calmette-Guerin (BCG) or chemotherapy agent instillation, is required to reduce the recurrence rate. The problem is these agents have very limited effect on the recurrence and often have environmental toxicities.
BCG is a potent intravesical therapy for superficial (non-invasive) bladder cancers, but the recurrence rate is still high. Although intravesical adjuvant therapies, such as BCG, Mitomycin-C (MMC), Epirubicin or the like, have been used in clinical practice, the recurrence rate is close to 50% (40% and 53% in BCG and chemotherapy, respectively) while the disease progression rate is 15% in the test groups. These results show poor therapeutic effect with less benefit. Moreover, patients may be reluctant to take these adjuvant therapies due to certain side effects, such as cystitis, fever, haematuria, or high urinary frequency.